The principle of QCM is used in methods for measuring the interaction between biological substances, such as DNA or proteins, and in measurements applying antigen-antibody reactions.
Conventional biosensors using QCM excite a piezoelectric element (quartz resonator or the like), which is a sensor, and continuously measure the resonance frequency, or continuously measure the frequency of the resonance point (the point where the impedance is lowest) using an impedance analyzer, and measure the amount of the substance adsorbed to the piezoelectric element surface by the frequency change.
The resonance frequency of the piezoelectric element (quartz resonator) immersed in the liquid fluctuates not only when the mass is changed, but also when the viscosity is changed. When the frequency fluctuation due to changes in mass is referred to as “mass effect,” and the frequency fluctuation due to viscosity fluctuation is referred to as “viscosity effect,” then, of the frequency fluctuations, the fluctuation amount due to the mass effect and the fluctuation amount due to the viscosity effect cannot be separated by the conventional approach of measuring only the fluctuations at the resonance frequency.
For example, when trying to examine the interaction between biological substances, such as DNA or proteins, by measuring frequency fluctuations, or when trying to examine antigen-antibody reactions by frequency fluctuations, then the viscosities of the sample injected into the measurement system and the employed buffer solution (biochemical buffer solution whose principal component are NaCl and KCl or the like) are different. As such, it becomes impossible to distinguish whether the measured frequency fluctuation value stems from the mass effect due to DNA and protein binding and antigen-antibody binding, or from the viscosity effect due to temperature changes or adding of sample substance, and thus an accurate measurement is impossible.
Regarding analysis technologies using piezoelectric resonators, the following related background art is known:
Patent Document 1: JPA 2002-148295
Patent Document 2: JPA 2002-156368
Patent Document 3: JPA H4-1554
The present invention has been made in order to solve the problems in the related art, and it is an object of the present invention to provide a technology for accurately determining mass changes of a piezoelectric resonator without being influenced by the viscosity effect.